Acute effects of paroxetine on genioglossus activity in obstructive sleep apnea

STUDY OBJECTIVE: To determine the acute effects of paroxetine on genioglossus activity during NREM sleep. DESIGN: A single dose of Paroxetine (40 mg) or placebo was administered four hours before bedtime on nights separated by one week in a double blind randomized crossover manner. The moving time average of genioglossus muscle activity (EMGgg) expressed as a percentage of maximum was measured using a mouthpiece electrode customized for each subject. The peak inspiratory and tonic values of EMGgg and the corresponding esophageal pressure deflections (DP) during the last three occluded breaths of obstructive apneas during NREM sleep were analyzed. SETTING: NA. PARTICIPANTS: 8 adult men with severe obstructive sleep apnea (OSA). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Paroxetine increased the peak inspiratory EMGgg (29.8+/-2.4 (SE) versus 24.4+/-2.7 % max, p<0.05) and peak EMGgg/DP ratio (0.78+/-0.12 versus 0.65+/-0.11 % max/cm H2O, p<0.01) but not the tonic EMGgg (11.6+/-0.9 versus 9.8+/-0.7 % max) nor the DP (39.4+/-2.2 versus 38.2+/-2.8 cm H2O). Linear regression analysis of the peak inspiratory EMGgg versus DP relationship showed that paroxetine increased the slope (0.62+/-0.11 versus 0.49+/-0.09 % max/cm H2O, p<0.01). However, the apnea + hypopnea index (paroxetine: 75.2+/-5.5 versus placebo: 73.7+/-6.9 events/hour) did not differ. CONCLUSIONS: Paroxetine augmented peak inspiratory genioglossus activity during NREM sleep but this effect was not sufficient to decrease the frequency of obstructive apnea in this group with severe OSA.     

Degree of arousal is most correlated with blood pressure reactivity during sleep in obstructive sleep apnea.

We investigated blood pressure (BP) reactivity of obstructive sleep apnea (OSA) during rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. The influences on BP reactivity of degree of arousal, the lowest O2 saturation (SaO2), and respiratory disturbance (RD) duration were compared. Ten normotensive or borderline hypertensive patients with OSA were studied with one-night polysomnography including non-invasive beat-to-beat BP monitoring (Finapres). We compared baseline BP, pre-apneic BP, and post-apneic BP during both REM and NREM sleep. Also, relationships between delta BP (post-apneic BP minus pre-apneic BP) and degree of arousal, the lowest SaO2, and RD duration were examined. During both REM and NREM sleep, pre-apneic BP was elevated compared with baseline BP. Post-apneic BP elevation was noted compared with pre-apneic BP. The degree of arousal was more significantly correlated with delta BP than the lowest SaO2. RD duration was hardly correlated with delta BP. Pre-apneic BP elevation seems to result from cumulation of sympathetic activation and sympathetic nervous system resetting. The correlation between delta BP and degree of arousal suggests that sympathetic activation causing post-apneic BP elevation may result mainly from an arousal response regardless of hypoxia.     

Sleep apnea and body position during sleep

In patients with obstructive sleep apnea, it is believed that body position influences apnea frequency. Sleeping in the lateral decubitus position often results in significantly fewer apneas, and some have recommended sleeping on the side as the major treatment intervention. Previous studies, although calculating apnea-hypopnea index (AHI) for supine and lateral decubitus positions, have not taken sleep stage into account. To examine the effect of both sleep stage and body position on apnea duration (AD) and frequency, we determined AHI and AD in all spontaneous body positions during rapid eye movement (REM) and non-REM (NREM) sleep by reviewing videotapes and polysomnograms from 11 overnight studies of 7 obese patients with severe sleep apnea. Consistent with previous work, AD was significantly longer in REM then in NREM (32.5 +/- 2.3 s versus 23.5 +/- 1.9 s; p less than 0.05). This difference persisted when adjusting for body position. AHI was greater on the back than on the sides (84.4 +/- 4.9/h versus 73.6 +/- 7.5/h, p less than 0.05), but after accounting for sleep stage, this difference remained only for NREM (103 +/- 4.8/h versus 80.3 +/- 9.2/h, p less than 0.05) and not for REM (83.6 +/- 5.3/h versus 71.1 +/- 4.2/h, p NS). Although reduced, AHI on the sides still remained clinically very high. Body position changed frequently throughout the night, but some patients spent little or no time on their back. We conclude that AD is longer in REM than NREM, regardless of position, and AHI is higher on the back only in NREM. As AHI remains very high on the sides, favoring the lateral decubitus position may not be as beneficial as previously thought in very obese patients. Less obese patients are more likely to benefit by position changes.     

The effects of ondansetron on sleep-disordered breathing in the English bulldog

Serotonin and serotoninergic drugs have significant effects on respiration, at many sites throughout the nervous system, and serotonin has been implicated in the pathogenesis of obstructive sleep apnea. Thus, understanding the serotoninergic mechanisms underlying respiratory control may help discover novel pharmacotherapies for sleep-disordered breathing. Ondansetron, a serotonin (5-HT) antagonist selective for the 5-HT3 receptor subtype has recently been shown to suppress sleep-related central apneas in rats, particularly in rapid-eye-movement (REM) sleep. To evaluate the potential of ondansetron in the treatment of obstructive sleep-disordered breathing, we have performed randomized trials of two doses of ondansetron (20 and 40 mg orally) and placebo (4 studies for each of the 3 conditions) in our animal model of obstructive sleep apnea, the English Bulldog. Ondansetron significantly reduced the respiratory disturbance index (RDI) in REM sleep from 24.15+/-4.85 events/hour at placebo to 11.01+/-1.56 events/hour with high dose treatment, n=4, p<0.05. In contrast, the effects of drug on the RDI in non-rapid-eye-movement (NREM) sleep (5.23+/-1.30 events/hour, placebo; 4.31+/-1.36, with 20 mg ondansetron and 2.89+/-1.30 with 40 mg ondansetron, n=4) were not significant. Ondansetron, however, had no effect on either sleep efficiency or sleep architecture, and there were no effects on either oxyhemoglobin saturation nadirs or on the sleep time with saturations <90%. Although a trend towards reduction in the latter measure of oxygenation was seen at the higher dose of ondansetron. These data suggest a therapeutic potential for ondansetron in obstructive sleep-disordered breathing, particularly REM sleep apnea.     

Effects of a lifestyle intervention on REM sleep‐related OSA severity in obese individuals with type 2 diabetes

The aim of this study was to determine if an intensive lifestyle intervention (ILI) reduces the severity of obstructive sleep apnea (OSA) in rapid‐eye movement (REM) sleep, and to determine if longitudinal changes in glycaemic control are related to changes in OSA severity during REM sleep over a 4‐year follow‐up. This was a randomized controlled trial including 264 overweight/obese adults with type 2 diabetes (T2D) and OSA. Participants were randomized to an ILI targeted to weight loss or a diabetes support and education (DSE) control group. Measures included anthropometry, apnea–hypopnea index (AHI) during REM sleep (REM‐AHI) and non‐REM sleep (NREM‐AHI) and glycated haemoglobin (HbA1c) at baseline and year 1, year 2 and year 4 follow‐ups. Mean baseline values of REM‐AHI were significantly higher than NREM‐AHI in both groups. Both REM‐AHI and NREM‐AHI were reduced significantly more in ILI versus DSE, but these differences were attenuated slightly after adjustment for weight changes. Repeated‐measure mixed‐model analyses including data to year 4 demonstrated that changes in HbA1c were related significantly to changes in weight, but not to changes in REM‐AHI and NREM‐AHI. Compared to control, the ILI reduced REM‐AHI and NREM‐AHI during the 4‐year follow‐up. Weight, as opposed to REM‐AHI and NREM‐AHI, was related to changes in HbA1c. The findings imply that weight loss from a lifestyle intervention is more important than reductions in AHI for improving glycaemic control in T2D patients with OSA.     

Effect of celiprolol treatment in hypertensive patients with sleep apnea.

The effects of a beta-blocker, celiprolol, on sleep and arterial blood pressure (BP) were evaluated during a single-blind study in seven hypertensive patients with sleep apnea. Diurnal ambulatory BP measurements with an automatic cuff-inflation device and polysomnography with simultaneous Finapres BP recording were performed separately on consecutive days at the end of two 21-day treatment periods involving placebo followed by celiprolol (200 mg/day). Age was 59 +/- 2.5 yr (m +/- sem) and body mass index 33.2 +/- 2.3 kg. m-2. Diurnal ambulatory BP was significantly lower with celiprolol than with placebo (systolic 139 +/- 4 vs 152 +/- 5 mmHg, diastolic 86 +/- 2 vs 96 +/- 2 mmHg). The apnea-hypopnea index was similar under celiprolol and placebo (48 +/- 7.4 vs 53 +/- 7.8, respectively), as were the total sleep time and percent of duration of the different sleep stages. Individual average BP values were significantly lower during REM sleep under celiprolol but remained similar under celiprolol and placebo in the other sleep stages. Variability of nocturnal BP (assessed by the SD of distribution of BP variations) was not affected by celiprolol. In conclusion, celiprolol which decreased daytime BP, did not affect sleep pattern or respiratory disturbances, or nocturnal BP variability related to apnea.     

Effect of expiratory positive airway pressure on sleep disordered breathing

STUDY OBJECTIVES: We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN: Observational physiology study PARTICIPANTS: We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS: The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION: In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.     

Acute Cardiovascular Changes with Obstructive Events in Children with Sleep Disordered Breathing

Study Objectives:

Obstructive apneas in adults are associated with acute changes in blood pressure (BP) and heart rate (HR) that may contribute to poor cardiovascular outcome. Children with sleep disordered breathing (SDB) are similarly at risk for cardiovascular complications. We aimed to test the hypothesis that BP and HR are augmented during obstructive events in children equivalent to levels reported in adults.

Design:

Beat-by-beat mean arterial pressure (MAP) and HR were analyzed over the course of obstructive events (pre, early, late, and post-event) during NREM and REM sleep and compared using 2-way ANOVA with post hoc analyses.

Setting:

Pediatric sleep laboratory.

Patients or Participants:

30 children (15M/15F) aged 7–12 y referred for investigation of SDB

Interventions:

N/A

Measurements and Results:

All children underwent overnight polysomnography with continuous BP recording. MAP and HR increased significantly from late to post event in both sleep states (mean ± SEM, NREM: MAP, 74 ± 3 to 93 ± 3 mm Hg; HR, 76 ± 2 to 97 ± 2 bpm. REM: MAP, 76 ± 3 to 89 ± 3 mm Hg; HR, 76 ± 2 to 91 ± 2 bpm. P < 0.05 for all). NREM sleep state and arousal from sleep were significant independent predictors of the magnitude of cardiovascular change from late to post event (P < 0.05 for all).

Conclusions:

Children with SDB experience significant changes in HR and BP during obstructive events with magnitudes that are similar to levels reported in adults. These changes are more pronounced during NREM sleep and with arousal. These acute cardiovascular changes may have important implications for poor cardiovascular outcome in children with OSA as repetitive cardiovascular perturbations may contribute to the development of hypertension.

Citation:

O''Driscoll DM; Foster AM; Ng ML; Yang JSC; Bashir F; Nixon GM; Davey MJ; Anderson V; Walker AM; Trinder J; Horne RSC. Acute cardiovascular changes with obstructive events in children with sleep disordered breathing. SLEEP 2009;32(10):1265-1271.     

Sleep state distribution of obstructive events in children: is obstructive sleep apnoea really a rapid eye movement sleep‐related condition?

Obstructive sleep apnoea (OSA) in children is commonly considered to occur predominantly in rapid eye movement (REM) sleep, but clinical experience suggests that this is not universally the case. We hypothesized that there would be a subgroup of children with OSA who have non‐REM (NREM) predominance of obstructive events and that these children share certain clinical characteristics. Thus, we aimed to compare the obstructive apnoea–hypopnoea index (OAHI) in REM versus NREM sleep and to assess factors influencing the distribution of events by sleep state. Polysomnography (PSG) recordings of 102 children aged 0–18 years with moderate to severe OSA (OAHI ≥5 h^?1) were reviewed. OAHI was calculated separately for REM and NREM sleep. A REM predominance index (RPI) was determined using log transformation [RPI = log (REM OAHI + 0.5) ? log (NREM OAHI + 0.5)] and compared with possible influencing factors using multiple linear regression. Analysis showed that obstructive events were more common in REM sleep (median REM OAHI 21.4 h^?1, median NREM OAHI 8.3 h^?1, P < 0.001). Mean RPI was significantly greater than zero (P = 0.003). However, a substantial minority of children (30.4%) had a higher NREM than REM OAHI. The factors that were related significantly to NREM predominance were older age (P = 0.02), higher arousal index (P < 0.001) and higher SpO₂ nadir (P < 0.001). Our findings demonstrate that while OSA is a REM sleep‐related problem in the majority of children, there is a significant subset of children with NREM predominance of obstructive events. This finding highlights the importance of considering sleep state distribution of events in studies of the pathophysiology and outcomes of OSA in childhood.     

Probabilistic sleep architecture models in patients with and without sleep apnea

Sleep fragmentation of any cause is disruptive to the rejuvenating value of sleep. However, methods to quantify sleep architecture remain limited. We have previously shown that human sleep-wake stage distributions exhibit multi-exponential dynamics, which are fragmented by obstructive sleep apnea (OSA), suggesting that Markov models may be a useful method to quantify architecture in health and disease. Sleep stage data were obtained from two subsets of the Sleep Heart Health Study database: control subjects with no medications, no OSA, no medical co-morbidities and no sleepiness (n = 374); and subjects with severe OSA (n = 338). Sleep architecture was simplified into three stages: wake after sleep onset (WASO); non-rapid eye movement (NREM) sleep; and rapid eye movement (REM) sleep. The connectivity and transition rates among eight 'generator' states of a first-order continuous-time Markov model were inferred from the observed ('phenotypic') distributions: three exponentials each of NREM sleep and WASO; and two exponentials of REM sleep. Ultradian REM cycling was accomplished by imposing time-variation to REM state entry rates. Fragmentation in subjects with severe OSA involved faster transition probabilities as well as additional state transition paths within the model. The Markov models exhibit two important features of human sleep architecture: multi-exponential stage dynamics (accounting for observed bout distributions); and probabilistic transitions (an inherent source of variability). In addition, the model quantifies the fragmentation associated with severe OSA. Markov sleep models may prove important for quantifying sleep disruption to provide objective metrics to correlate with endpoints ranging from sleepiness to cardiovascular morbidity.     

Relations between sleep stage, posture and effective nasal CPAP levels in OSA.

A retrospective analysis of positional data from 100 male patients with obstructive sleep apnea (OSA) was conducted to determine whether or not 1) the degree of positional dependency was similar in rapid eye movement (REM) compared to non-REM (NREM) sleep, 2) positional dependency correlated with effective levels of nasal continuous positive airway pressure (CPAP) and 3) patients with positional OSA preferentially avoided sleeping in the supine position. The apnea-hypopnea index (AHI) was scored separately for sleep state (NREM and REM) and for posture [off back (AHI-O) and on back (AHI-B)]. The ratio of AHI-O/AHI-B was used to define positional OSA as AHI-O/AHI-B less than or equal to 0.50 (P group) and nonpositional OSA as 0.50 less than AHI-O/AHI-B (NP group). A group of 31 patients who had sufficient sleep time in NREM and REM sleep in both sleep postures was selected. In this group 9 out of 22 subjects who showed positional dependency during NREM sleep became nonpositional during REM sleep (0.05 less than p less than 0.10). The mean effective nasal CPAP level was slightly, but significantly, lower in the P group than in the NP group (8.0 versus 9.1 cm H2O; p less than 0.05). In addition, a correlation between AHI and effective nasal CPAP levels was found (r = 0.491; p = 0.0001). The P group had less supine sleep time (SST) than the NP group (32% versus 45% of total sleep; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Obstructive sleep apnea is associated with increased arterial stiffness in severe obesity

Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non‐invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy‐two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42 ± 7 kg m^?2), without obstructive sleep apnea (non‐OSA) 25 (body mass index 40 ± 5 kg m^?2)] were characterised using anthropometric, respiratory and cardio‐metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non‐OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P < 0.001), with significantly higher systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P = 0.004) than patients without obstructive sleep apnea (non‐OSA). Arterial stiffness correlated with mean arterial blood pressure (P = 0.003) and obstructive sleep apnea severity (apnea–hypopnea index; P < 0.001). apnea–hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.     

Noninvasive determination of brain tissue oxygenation during sleep in obstructive sleep apnea: a near-infrared spectroscopic approach

STUDY OBJECTIVES: Recurrent apneas and hypoxemia during sleep in obstructive sleep apnea (OSA) are associated with profound changes in cerebral blood flow to the extent that cerebral autoregulation may be insufficient to protect the brain. Since the brain is sensitive to hypoxia, the cerebrovascular morbidity seen in OSA could be due to chronic, cumulative effects of intermittent hypoxia. Near-infrared spectroscopy (NIRS) has the potential to noninvasively monitor brain tissue oxygen saturation (SO2), and changes in concentration of oxyhemoglobin [O2Hb], deoxyhemoglobin [HHb] and total hemoglobin [tHb] with real-time resolution. We hypothesized that brain tissue oxygenation would be worse during sleep in OSA relative to controls and sought to determine the practical use of NIRS in the sleep laboratory. DESIGN: We evaluated changes in brain tissue oxygenation using NIRS during overnight polysomnography. SETTING: Studies were conducted at University of Illinois, Chicago and Carle Hospital, Urbana, Illinois. PATIENTS: Nineteen subjects with OSA and 14 healthy controls underwent continuous NIRS monitoring during polysomnography. MEASUREMENTS AND RESULTS: We observed significantly lower indexes of brain tissue oxygenation (SO2: 57.1 +/- 4.9 vs. 61.5 +/- 6.1), [O2Hb]: 22.8 +/- 7.7 vs. 31.5 +/- 9.1, and [tHb]: 38.6 +/- 11.2 vs. 48.6 +/- 11.4 micromol/L) in OSA than controls (all P < 0.05). However, multivariate analysis showed that the differences might be due to age disparity between the two groups. CONCLUSIONS: NIRS is an effective tool to evaluate brain tissue oxygenation in OSA. It provides valuable data in OSA assessment and has the potential to bridge current knowledge gap in OSA.     

Complex sleep apnea syndrome: is it a unique clinical syndrome?

STUDY OBJECTIVES: Some patients with apparent obstructive sleep apnea hypopnea syndrome (OSAHS) have elimination of obstructive events but emergence of problematic central apneas or Cheyne-Stokes breathing pattern. Patients with this sleep-disordered breathing problem, which for the sake of study we call the "complex sleep apnea syndrome," are not well characterized. We sought to determine the prevalence of complex sleep apnea syndrome and hypothesized that the clinical characteristics of patients with complex sleep apnea syndrome would more nearly resemble those of patients with central sleep apnea syndrome (CSA) than with those of patients with OSAHS. DESIGN: Retrospective review SETTING: Sleep disorders center. PATIENTS OR PARTICIPANTS: Two hundred twenty-three adults consecutively referred over 1 month plus 20 consecutive patients diagnosed with CSA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Prevalence of complex sleep apnea syndrome, OSAHS, and CSA in the 1-month sample was 15%, 84%, and 0.4%, respectively. Patients with complex sleep apnea syndrome differed in gender from patients with OSAHS (81% vs 60% men, p < .05) but were otherwise similar in sleep and cardiovascular history. Patients with complex sleep apnea syndrome had fewer maintenance-insomnia complaints (32% vs 79%; p < .05) than patients with CSA but were otherwise not significantly different clinically. Diagnostic apnea-hypopnea index for patients with complex sleep apnea syndrome, OSAHS, and CSA was 32.3 +/- 26.8, 20.6 +/- 23.7, and 38.3 +/- 36.2, respectively (p = .005). Continuous positive airway pressure suppressed obstructive breathing, but residual apnea-hypopnea index, mostly from central apneas, remained high in patients with complex sleep apnea syndrome and CSA (21.7 +/- 18.6 in complex sleep apnea syndrome, 32.9 +/- 30.8 in CSA vs 2.14 +/- 3.14 in OSAHS; p < .001). CONCLUSIONS: Patients with complex sleep apnea syndrome are mostly similar to those with OSAHS until one applies continuous positive airway pressure. They are left with very disrupted breathing and sleep on continuous positive airway pressure. Clinical risk factors don't predict the emergence of complex sleep apnea syndrome, and best treatment is not known.     

Night-to-night alterations in sleep apnea type in patients with heart failure

In patients with heart failure, apnea type can shift overnight from mainly obstructive to mainly central in association with reductions in PCO(2) and increases in periodic breathing cycle length, indicative of a fall in cardiac output. We hypothesized that the predominant apnea type could also vary from one night to another in association with alterations in PCO(2) and cycle length. We studied 12 men with heart failure in whom the predominant apnea type changed from one night to the next over periods of at least 1 month, and two groups with either predominantly obstructive or central sleep apnea (OSA or CSA) in whom apnea type remained stable over time. In patients with unstable apnea type (n = 12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during nights with predominantly central than nights with predominantly obstructive apnea. In contrast, in both the stable central (n = 8, duration between sleep studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length changed significantly between the baseline and follow-up sleep studies. We conclude that in some patients with heart failure, OSA and CSA are part of a spectrum of periodic breathing that can shift over time in association with alterations in PCO(2), cycle length and probably cardiac function.     

Pulse transit time and blood pressure changes following auditory-evoked subcortical arousal and waking of infants

STUDY OBJECTIVES: To establish a normal range of data in 3-month-old infants in relation to changes in cardiovascular measurements, with particular reference to pulse transit time (PTT), following subcortical arousals and awakenings from sleep. DESIGN: Prospective study. SETTING: Sleep laboratory, Dunedin Hospital PARTICIPANTS: Twenty healthy infants aged 9-12 weeks. METHODS: Nap studies were performed using a standard polysomnographic setup with the addition of a Portapres blood pressure (BP) cuff (wrist application) and a piezoelectric sensor on the foot. PTT was measured from the ECG-R waveform to the arrival of the pulse peripherally. Infants were exposed to white noise from 50 to 100 dB at 10 dB intervals within REM and NREM sleep. RESULTS: Awakening thresholds were higher (P = 0.01) in NREM (>90 dB) than REM sleep (mean +/- SD; 74.3 +/- 9.4dB). Subcortical thresholds were always 10 dB below waking thresholds. Following awakening, there was an immediate increase in HR, SBP, and DBP of 21%, 14%, and 17%, respectively, and a 13% decrease in PTT returning to baseline within 25-30 seconds. PTT at baseline measured 140 +/- 11 and 139 +/- 9 msec in NREM and REM sleep, respectively, and decreased approximately 20 msec with waking. PTT changes were negatively correlated with heart rate (HR) but not BP, although a trend was evident. CONCLUSIONS: At 3 months of age, infants provoked to arouse from sleep showed PTT changes that inversely mimicked BP trends, suggesting that PTT could be useful in infant studies as a marker for autonomic perturbations that occur during sleep in both clinical and research settings.     

Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial

STUDY OBJECTIVE: To investigate the short-term effect (4 weeks) of oral appliance therapy for obstructive sleep apnea on blood pressure. DESIGN: Randomized, controlled, crossover trial. SETTING: Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS: Sixty-one patients diagnosed with obstructive sleep apnea on polysomnography (apnea hypopnea index > or = 10 per hour and at least 2 of the following symptoms--daytime sleepiness, snoring, witnessed apneas, fragmented sleep; age > 20 years; and minimum mandibular protrusion of 3 mm). INTERVENTION: A mandibular advancement splint (MAS) and control oral appliance for 4 weeks each. MEASUREMENTS AND RESULTS: Polysomnography and 24-hour ambulatory blood pressure monitoring were carried out at baseline and following each 4-week intervention period. Patients showed a 50% reduction in mean apnea hypopnea index with MAS compared with the control and a significant improvement in both minimum oxygen saturation and arousal index. There was a significant reduction with the MAS in mean (+/- SEM) 24-hour diastolic blood pressure (1.8 +/- 0.5 mmHg) compared with the control (P = .001) but not in 24-hour systolic blood pressure. Awake blood-pressure variables were reduced with the MAS by an estimated mean (+/- SEM) of 3.3 +/- 1.1 mmHg for systolic blood pressure (P = .003) and 3.4 +/- 0.9 mmHg for diastolic blood pressure (P < .0001). There was no significant difference in blood pressure measured asleep. CONCLUSION: Oral appliance therapy for obstructive sleep apnea over 4 weeks results in a reduction in blood pressure, similar to that reported with continuous positive airway pressure therapy.     

Excitation of medullary respiratory neurons in REM sleep

STUDY OBJECTIVE: To study tonic inputs to medullary respiratory neurons during rapid eye movement (REM) sleep. DESIGN: Single medullary-respiratory-neuron recordings during sleep with spontaneous breathing and during apnea caused by mechanical hyperventilation. SETTING: Academic laboratory. SUBJECTS: Three tracheostomized adult cats implanted for polysomnography and extracellular microelectrode recordings. Intervention: Single medullary-respiratory-neuron recordings during spontaneous breathing and mechanical hyperventilation to apnea during non-REM (NREM) and REM sleep. RESULTS: Most but not all respiratory cells of all types (pre-inspiratory, decrementing, augmenting and late inspiratory, phase-spanning, and expiratory) were more active in REM sleep than in NREM sleep during both spontaneous breathing and apnea induced by mechanical hyperventilation. The mean discharge rate of the cells during spontaneous breathing in NREM sleep was 16.7 impulses per second and in REM sleep was 26.5 impulses per second. During ventilator-induced apnea, the mean rates were 10 impulses per second in NREM sleep and 17.5 per second during REM sleep. The increase in activity in REM sleep occurred after a delay of several seconds from the onset of REM sleep. Respiratory cells were excited at times individually and at other times simultaneously in either a reciprocal or nonreciprocal pattern. The degree of excitation of a neuron in REM sleep during ventilator-induced apnea was proportional to the degree of excitation of the neuron in REM sleep during spontaneous breathing. CONCLUSION: Medullary respiratory neurons are excited individually and collectively in REM sleep. The excitation occurs with a delay after the onset of the state and can stimulate and/or disorganize breathing.     

Measurement of changes in cytochrome oxidase redox state during obstructive sleep apnea using near-infrared spectroscopy

STUDY OBJECTIVES: To use near-infrared spectroscopy to investigate the effect of obstructive sleep apnea on cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain. DESIGN: Observational study. SETTING: Teaching hospital sleep unit. PATIENTS: Subjects with diagnosed moderate to severe obstructive sleep apnea were recruited from the sleep clinic. INTERVENTIONS: Subjects were invited to attend 2 daytime sleep-study sessions, which included near-infrared monitoring of cerebral oxygenation and cytochrome-oxidase oxidation state. In addition, in study session 1, full polysomnography was performed (8 subjects, 303 apneas), and in study session 2, arterial oxygen saturation, cerebral blood flow velocity, and blood pressure were monitored (7 subjects, 287 apneas). MEASUREMENTS AND RESULTS: In study session 1, mean (+/- SD) cytochrome-oxidase changes ranged from 0.48 +/- 0.08 microM to 0.13 +/- 0.05 microM. The magnitude of cytochrome-oxidase change correlated significantly with the magnitude of change in the cerebral tissue oxygenation index (P < .001). In study session 2, there were significant correlations between arterial oxygen-saturation changes and cytochrome-oxidase redox changes and between Doppler cerebral blood flow velocity changes and cytochrome-oxidase redox changes (P < .001 and P = .001, respectively). CONCLUSIONS: Changes in directly measured cerebral tissue saturation and changes in arterial saturation and cerebral blood flow velocity (the 2 main factors affecting cerebral oxygenation) are associated with changes in cytochrome-oxidase oxidation state. The reduced cerebral oxygenation that occurs during obstructive sleep apnea is associated with changes in the intracellular redox state.     

Comparison of pleural pressure and transcutaneous diaphragmatic electromyogram in obstructive sleep apnea syndrome

STUDY OBJECTIVES: Based on studies of the impact of esophageal pressure on cardiovascular variables during sleep, this signal can be used to refine the severity level in the clinical diagnosis of obstructive sleep apnea syndrome. We hypothesized that relative changes in diaphragmatic electromyogram (EMG) can reflect short-term changes in esophageal pressure durng obstructive apneas and hypopneas. DESIGN: Diaphragmatic EMG was sampled at 0.25 kHz; diaphragmatic EMG waveform was band-pass filtered and digitally converted; the electrocardiogram artifact was eliminated; using a gating procedure, the waveform was fast-Fourier transformed and digitally rectified; and a moving average of 200 milliseconds was calculated. For each inspiratory effort during apnea or hypopnea, we calculated maximum diaphragmatic EMG and esophageal pressure. Data were normalized calculating the percentage difference between the first obstructed and each subsequent inspiratory effort during the respiratory event. SETTING: Sleep disorders laboratory. PATIENTS: 9 patients with moderate obstructive sleep apnea syndrome presenting with apneas and hypopneas during sleep. INTERVENTION: None. MEASUREMENTS AND RESULTS: 861 respiratory events were scored, and the evolution between esophageal pressure and diaphragmatic EMG were compared. Normalized data showed a good correlation between the 2 measures during apneas and hypopneas. There was a significant difference between the percentage increase in esophageal pressure and diaphragmatic EMG for apneas and hypopneas (esophageal pressure, apnea: 118.1% +/- 118.5%, hypopnea: 76.1% +/- 74.3%, P = .000; diaphragmatic EMG, 123.5% +/- 131.7%, hypopnea: 73.3% +/- 74.2%, P = .000). No significant differences for apnea or hypopnea were noted between the 2 measures under investigation. CONCLUSION: Diaphragmatic EMG may be clinically useful to describe relative changes in respiratory effort under conditions of apnea and hypopnea during sleep and to reliably dissociate central from obstructive events where esophageal pressure monitoring is not readily available.